Large banks of archived human tumor tissues including cancer biopsies harbor enormous amounts of disease relevant information that may facilitate development of novel therapeutic approaches and assist in our basic understanding of fundamental biological processes. However, the resource is clearly underused, due to a number of technical challenges associated with the retrieval of molecular information hidden in the RNA, DNA and proteins locked inside the samples. Current microdissection platforms (especially those with single cell resolution) are typically sample specific, complex, expensive, and overly dependent on manual user intervention at key steps. Despite the need, these limitations make integration within standard lab/clinical sample processing workflows difficult. Rapid cell- and region-specific nucleic acid extraction from formalin fixed tumor biopsies and archived tissue samples is perhaps one of the most desirable and technically challenging applications. To facilitate the use of the archived and clinical tissue specimens, we propose to develop an automated platform (AutopicK-MTM) for high-throughput fixed tissue microdissection. Automatic molecular retrieval from archived and clinical FFPE tissue samples will be based on our recently developed cell and tissue acquisition (CTAS) technology, using GE?s proprietary approach for rapid extraction of histological regions of interest (ROIs) from FFPE tissues. Importantly, the collected FFPE ROIs are optimized for direct molecular interrogation and compatible with most enzymatic reactions including protocols used for Next Generation Sequencing (NGS). The proposed instrument will feature auto-calibration, ROI auto recognition, collection and dispensing into multiwell plate formats. Our preliminary studies convincingly demonstrate that sample collection may be performed with cellular resolution, with a tissue dissociation step that ensures compatibility of isolated DNA with a range of downstream protocols including amplification, labeling and sequencing. As both NeuroInDx and GEGR technologies can be implemented at low cost, AutopicK-MTM will have a serious price advantage over existing competitors. Moreover, the new instrument will remain compatible with fresh frozen, live cell, and fixed single cell samples, making the AutopicK-MTM the most versatile single cell acquisition and tissue microdissection platform on the market. This Fast Track application will test all critical parameters of the proposed approach including tissue processing and initial instrument architecture in Phase I. Commercial prototype of the proposed instrument and a complete workflow will be developed and validated in Phase II.